While previous studies by us and others have shown that ER stress and subsequent IRE1 activation are causally associated with atherosclerosis progression, the mechanism by which IRE1 contributes to the disease pathogenesis has remained elusive (Erbay et al, 2009; Zhou & Tabas, 2013; Tufanli et al, 2017). This evidence concerns the gene ERN1 and atherosclerosis.